ABSTRACT
This work aims to explore the gas permeation performance of two newly-designed ionic liquids, [C2mim][CF3BF3] and [C2mim][CF3SO2C(CN)2], in supported ionic liquid membranes (SILM) configuration, as another effort to provide an overall insight on the gas permeation performance of functionalized-ionic liquids with the [C2mim]+ cation. [C2mim][CF3BF3] and [C2mim][CF3SO2C(CN)2] single gas separation performance towards CO2, N2, and CH4 at T = 293 K and T = 308 K were measured using the time-lag method. Assessing the CO2 permeation results, [C2mim][CF3BF3] showed an undermined value of 710 Barrer at 293.15 K and 1 bar of feed pressure when compared to [C2mim][BF4], whereas for the [C2mim][CF3SO2C(CN)2] IL an unexpected CO2 permeability of 1095 Barrer was attained at the same experimental conditions, overcoming the results for the remaining ILs used for comparison. The prepared membranes exhibited diverse permselectivities, varying from 16.9 to 22.2 for CO2/CH4 and 37.0 to 44.4 for CO2/N2 gas pairs. The thermophysical properties of the [C2mim][CF3BF3] and [C2mim][CF3SO2C(CN)2] ILs were also determined in the range of T = 293.15 K up to T = 353.15 K at atmospheric pressure and compared with those for other ILs with the same cation and anion's with similar chemical moieties.
ABSTRACT
Angiotensin II (Ang II) may contain a charge relay system (CRS) involving Tyr/His/carboxylate, which creates a tyrosinate anion for receptor activation. Energy calculations were carried out to determine the preferred geometry for the CRS in the presence and absence of the Arg guanidino group occupying position 2 of Ang II. These findings suggest that Tyr is preferred over His for bearing the negative charge and that the CRS is stabilized by the guanidino group. Recent crystallography studies provided details of the binding of nonpeptide angiotensin receptor blockers (ARBs) to the Ang II type 1 (AT1) receptor, and these insights were applied to Ang II. A model of binding and receptor activation that explains the surmountable and insurmountable effects of Ang II analogues sarmesin and sarilesin, respectively, was developed and enabled the discovery of a new generation of ARBs called bisartans. Finally, we determined the ability of the bisartan BV6(TFA) to act as a potential ARB, demonstrating similar effects to candesartan, by reducing vasoconstriction of rabbit iliac arteries in response to cumulative doses of Ang II. Recent clinical studies have shown that Ang II receptor blockers have protective effects in hypertensive patients infected with SARS-CoV-2. Therefore, the usage of ARBS to block the AT1 receptor preventing the binding of toxic angiotensin implicated in the storm of cytokines in SARS-CoV-2 is a target treatment and opens new avenues for disease therapy.
Subject(s)
Angiotensin II/metabolism , Angiotensin Receptor Antagonists/chemistry , Angiotensin Receptor Antagonists/pharmacology , COVID-19 Drug Treatment , Drug Discovery , Receptor, Angiotensin, Type 1/metabolism , Angiotensin II/analogs & derivatives , Animals , COVID-19/metabolism , Crystallography, X-Ray , Humans , Hypertension/drug therapy , Hypertension/metabolism , Male , Models, Molecular , Rabbits , Receptor, Angiotensin, Type 1/chemistry , Vasoconstriction/drug effectsABSTRACT
This study examined the structure activity relationship of NH(3)-Phe-Glu-Gly-COO(-) (FEG), a potent inhibitor of intestinal anaphylaxis. The inhibition by FEG analogues of antigen-provoked contractions of isolated ileal segments obtained from ovalbumin-sensitized rats was determined and molecular modeling performed. A combination of aromaticity of the first residue, minimal extension of the carboxyl group on residue 2, and underivatized N and C termini were essential for biological activity. FEG, WEG, WDG and the d-enantiomeric forms of FEG (feG) and YEG (yeG) retained biological activity. By considering dipole moments, the structural and conformational features critical to biological activity were established as the glutamyl-carboxyl group/Phe side chain and carboxyl/amino termini interactions. Analysis of Ramachandran plots for position 1 sidechains indicate that mobility of the aromatic sidechain must be restricted to retain biological activity. The anti-anaphylactic effects of FEG, characterized by specific structural and conformational restrictions, indicate a selective interaction with a receptor for this peptide in the intestine.
